Neurobehavior and Brain Connectivity in Post COVID-19 Patients

NCT05307575 | Completed

• 1 other identifier: 202111-30-31-32 Fundació La Ma
• Study Type: observational
• Target: 630
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 neurological effects can generate long-term neurobehavioral dysfunction. Our main objective is to examine the impact of COVID-19 on neurobehavior and its relationship with illness severity. Besides, we aim to study structural and functional brain connectivity in a subsample of middle-aged post-COVID-19 individuals. Finally, we aim to develop predictive models of neurobehavioural evolution in post-COVID-19 based on multimodal data.

Conditions

Post-COVID Syndrome

Keywords

COVID-10; Cognition; Mental Health; Neuroimage; Machine Learning

Outcome Measures

Primary Outcomes (12)

• Differences between groups in auditory attention

  Auditory attention is measured with Digit Span Forward. Participants are asked to repeat numbers in the same order as read aloud by the examiner. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in working memory

  Working memory is measured with Digit Span Backward. Participants are asked to repeat the numbers in the reverse order of that presented by the examiner. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in language

  Language is measured with the Boston Naming Test. It consists of 60 line drawings of objects of graded difficulty, ranging from very common things to less familiar objects. The total score is the sum of correct answers. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in verbal memory

  Verbal memory is measured with the Auditory Verbal Learning Test (AVLT). It is a word-learning test where five presentations of a 15-word list are given, each followed by an attempted recall. This is followed by a second 15-word interference list (list B), followed by recall of list A. Delayed recall and recognition are also tested. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in visual memory

  Visual memory is measured with the Rey-Osterrieth Complex Figure (ROCF) test. The participants are asked to copy complex geometric shapes and then reproduce them from memory. A delayed recall is also tested. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in psychomotor speed

  Processing speed is measured with Coding subtest of WAIS. Participants are asked to use a key to put in the appropriate symbols for a list of numbers. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in perceptual reasoning

  Perceptual reasoning is measured with Matrix reasoning subtest of WAIS. Participants are asked to choose which of some possible options the missing picture is from matrix of abstract pictures. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in executive function

  A composite score is made with the z-scores of phonemic (sum of the three letters) and semantic fluency, Trail Making Test B (time) and STROOP test (color-word interference total items in 120 seconds).

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in social cognition

  Social cognition is measured with the Reading the Mind in the Eyes Test. Participants are asked to choose the emotional state that best describes the eyes, choosing between one of four possible emotions in the 36 photographs of male and female eyes depicting emotional states. Higher scores mean a better outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in anxiety

  Anxiety is measured with the 7-item Generalized Anxiety Disorder Scale (GAD-7), a Likert-type scale with questions ranging from "not at all" (0 points) to "nearly every day" (3 points). The maximum score is 24. Higher scores mean a worse outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in depression

  Depression is measured with the Patient Health Questionnaire-9 (PHQ-9) which scores each of the 9 DSM-IV criteria as "not at all" (0 points) to "nearly every day" (3 points). Higher scores mean a worse outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in Post-traumatic Stress Disorder

  Post-Traumatic Stress Disorder is measured with The Post-Traumatic Stress Disorder Checklist (PCL-5), a 20-item questionnaire corresponding to the DSM-5 symptom criteria for PTSD, which scores each criterion as "not at all" (0 points) to "extremely" (4 points). The ratings of items are added together to calculate the total score (range=0-80). Higher scores mean a worse outcome.

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

Secondary Outcomes (13)

• Differences between groups in Fatigue

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in Quality of Life

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in White Matter integrity

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in brain Volumetry

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

• Differences between groups in Resting-state connectivity

  At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

Study Arms (3)

Post-COVID syndrome (PCS) Severe COVID-19

Severe COVID-19 with PCS with cognitive complains

Post-COVID syndrome (PCS) Mild COVID-19

Mild COVID-19 with PCS with cognitive complains

Controls

Healthy adult controls

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

PCS from severe and mild COVID-19 group will be recruited in hospital and primary care services. The control population will be searched in the general population through primary care centers, the media, social networks, and they will be offered to participate in the study without remuneration.

You may qualify if:

• Confirmed diagnosis of COVID-19 according to WHO interim with signs and symptoms of the severe disease during the acute phase
• Presence of cognitive complaints after COVID-19 diagnosis
• Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki

You may not qualify if:

• Participants have symptoms of delirium according to Delirium Rating Scale-revised 98
• Established diagnosis before COVID-19 disease of psychiatric, neurological, neurodevelopmental disorder or systemic pathologies are known to cause cognitive deficits
• Motor or sensory alterations that impede the neuropsychological examination
• Participants with a metal prosthesis (for MRI studies)
• Subjects suffering from claustrophobia or requiring sedation due to high anxiety (for MRI studies)
• PCS from MILD COVID-19 group
• Confirmed diagnosis of MILD COVID-19 according to WHO interim
• Presence of cognitive complaints after COVID-19 diagnosis
• Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki
• Established diagnosis before COVID-19 disease of psychiatric, neurological, neurodevelopmental disorder or systemic pathologies are known to cause cognitive deficits
• Motor or sensory alterations that impede the neuropsychological examination
• Participants with a metal prosthesis (for MRI studies)
• Subjects suffering from claustrophobia or requiring sedation due to high anxiety (for MRI studies)
• Healthy adult CONTROL group
• Healthy people who have not had COVID-19

Sponsors & Collaborators

• Consorci Sanitari de Terrassa: lead
• University of Barcelona: collaborator
• Universitat Politècnica de Catalunya: collaborator

Study Sites (1)

Consorci Sanitari de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Related Publications (5)

• Carreras-Vidal L, Pacheco-Jaime L, Ariza M, Cano N, Garolera M, Garcia-Vicente C, Roura I, Capdevila-Lacasa C, Oltra J, Pardo J, Martin-Barcelo C, Campabadal A, Sala-Llonch R, Bargallo N, Barrue C, Bejar J, Cortes CU, Junque C; NAUTILUS-Project Collaborative Group; Segura B. Functional brain abnormalities in post COVID-19 condition and their relationship with cognition. Sci Rep. 2025 Jul 1;15(1):22259. doi: 10.1038/s41598-025-00739-3.

  PMID: 40595626 DERIVED

• Pacheco-Jaime L, Garcia-Vicente C, Ariza M, Cano N, Garolera M, Carreras-Vidal L, Roura I, Capdevila-Lacasa C, Oltra J, Pardo J, Martin-Barcelo C, Campabadal A, Sala-Llonch R, Bargallo N, Barrue C, Bejar J, Cortes CU, Junque C, Segura B; NAUTILUS-Project Collaborative Group. Structural brain changes in post-COVID condition and its relationship with cognitive impairment. Brain Commun. 2025 Feb 12;7(1):fcaf070. doi: 10.1093/braincomms/fcaf070. eCollection 2025.

  PMID: 40008326 DERIVED

• Ariza M, Bejar J, Barrue C, Cano N, Segura B; NAUTILUS Project Collaborative Group; Cortes CU, Junque C, Garolera M. Cognitive reserve, depressive symptoms, obesity, and change in employment status predict mental processing speed and executive function after COVID-19. Eur Arch Psychiatry Clin Neurosci. 2025 Jun;275(4):973-989. doi: 10.1007/s00406-023-01748-x. Epub 2024 Jan 29.

  PMID: 38285245 DERIVED

• Ariza M, Cano N, Segura B, Adan A, Bargallo N, Caldu X, Campabadal A, Jurado MA, Mataro M, Pueyo R, Sala-Llonch R, Barrue C, Bejar J, Cortes CU; NAUTILUS Project Collaborative Group; Garolera M, Junque C. COVID-19 severity is related to poor executive function in people with post-COVID conditions. J Neurol. 2023 May;270(5):2392-2408. doi: 10.1007/s00415-023-11587-4. Epub 2023 Mar 20.

  PMID: 36939932 DERIVED

• Ariza M, Cano N, Segura B, Adan A, Bargallo N, Caldu X, Campabadal A, Jurado MA, Mataro M, Pueyo R, Sala-Llonch R, Barrue C, Bejar J, Cortes CU; NAUTILUS-Project Collaborative Group; Junque C, Garolera M. Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints. Front Aging Neurosci. 2022 Oct 20;14:1029842. doi: 10.3389/fnagi.2022.1029842. eCollection 2022.

  PMID: 36337708 DERIVED

MeSH Terms

Conditions

Psychological Well-Being

Condition Hierarchy (Ancestors)

Personal Satisfaction; Behavior

Study Officials

• Maite Garolera, PhD

  Consorci Sanitari de Terrassa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of the Neuropsychology Unit and Director of the Brain, Cognition, and Behavior Research Group (C3-CST) of CST.

Study Record Dates

• First Submitted: March 31, 2022
• First Posted: April 1, 2022
• Study Start: October 1, 2021
• Primary Completion: September 15, 2024
• Study Completion: September 15, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)